Lang S, Hilsabeck TA, Wilson KA, Sharma A, Bose N, Brackman DJ, Beck JN, Chen L, Watson MA, Killilea DW, Ho S, Kahn A, Giacomini K, Stoller ML, Chi T, Kapahi P. A conserved role of the insulin-like signaling pathway in diet-dependent uric acid pathologies in Drosophila melanogaster. PLoS Genet. 2019 Aug 15;15(8):e1008318. PubMed PMID: 31415568; PubMed Central PMCID: PMC6695094.
From the abstract: "Elevated uric acid (UA) is a key risk factor for many disorders, including metabolic syndrome, gout and kidney stones. ... In humans, elevated UA levels resulted from the loss of the of the urate oxidase (Uro) gene ... we established a Drosophila melanogaster model with reduced expression of the orthologous Uro gene to study the pathogenesis arising from elevated UA. Reduced Uro expression in Drosophila resulted in elevated UA levels, accumulation of concretions in the excretory system, and shortening of lifespan ..."
Showing posts with label Kidney stones. Show all posts
Showing posts with label Kidney stones. Show all posts
Monday, September 30, 2019
Monday, June 24, 2019
Drugs, stones, and flies -- high-throughput screen in fly disease model identifies potential therapeutic for prevention of kidney stones
Ali SN, Dayarathna TK, Ali AN, Osumah T, Ahmed M, Cooper TT, Power NE, Zhang D, Kim D, Kim R, St Amant A, Hou J, Tailly T, Yang J, Luyt L, Spagnuolo PA, Burton JP, Razvi H, Leong HS. Drosophila melanogaster as a function-based high-throughput screening model for antinephrolithiasis agents in kidney stone patients. Dis Model Mech. 2018 Nov 16;11(11). pii: dmm035873. doi: 10.1242/dmm.035873. PubMed PMID: 30082495; PubMed Central PMCID: PMC6262805.
Abstract: "Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper."
Abstract: "Kidney stone disease involves the aggregation of stone-forming salts consequent to solute supersaturation in urine. The development of novel therapeutic agents for this predominantly metabolic and biochemical disorder have been hampered by the lack of a practical pre-clinical model amenable to drug screening. Here, Drosophila melanogaster, an emerging model for kidney stone disease research, was adapted as a high-throughput functional drug screening platform independent of the multifactorial nature of mammalian nephrolithiasis. Through functional screening, the therapeutic potential of a novel compound commonly known as arbutin that specifically binds to oxalate, a key component of kidney calculi, was identified. Through isothermal titration calorimetry, high-performance liquid chromatography and atomic force microscopy, arbutin was determined to interact with calcium and oxalate in both free and bound states, disrupting crystal lattice structure, growth and crystallization. When used to treat patient urine samples, arbutin significantly abrogated calculus formation in vivo and outperformed potassium citrate in low pH urine conditions, owing to its oxalate-centric mode of action. The discovery of this novel antilithogenic compound via D. melanogaster, independent of a mammalian model, brings greater recognition to this platform, for which metabolic features are primary outcomes, underscoring the power of D. melanogaster as a high-throughput drug screening platform in similar disorders. This is the first description of the use of D. melanogaster as the model system for a high-throughput chemical library screen. This article has an associated First Person interview with the first authors of the paper."
Monday, December 11, 2017
Diet-based Drosophila model of kidney stones
Chung VY, Turney BW. A Drosophila genetic model of nephrolithiasis: transcriptional changes in response to diet induced stone formation. BMC Urol. 2017 Nov 28;17(1):109. PMID: 29183349; PMCID: PMC5706311.
From the abstract: "... We have used Drosophila as a genetic model to study the transcriptional response to stone formation secondary to dietary manipulation. ... Wild-type male flies were raised on standard medium supplemented with lithogenic agents: control, sodium oxalate (NaOx) and ethylene glycol (EG). ... Crystal formation was visualized in 20%(±2.2) of flies on control diet, 73%(±3.6) on NaOx diet and 84%(±2.2) on EG diet. ... Fifty-eight genes were differentially expressed (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. ... This genetic model could be potentially used to identify the candidate genes that influence stone risk hence providing more insight to the pathogenesis of human stone disease."
From the abstract: "... We have used Drosophila as a genetic model to study the transcriptional response to stone formation secondary to dietary manipulation. ... Wild-type male flies were raised on standard medium supplemented with lithogenic agents: control, sodium oxalate (NaOx) and ethylene glycol (EG). ... Crystal formation was visualized in 20%(±2.2) of flies on control diet, 73%(±3.6) on NaOx diet and 84%(±2.2) on EG diet. ... Fifty-eight genes were differentially expressed (FDR <0.05, p < 0.05) in NaOx diet and 20 genes in EG diet. ... This genetic model could be potentially used to identify the candidate genes that influence stone risk hence providing more insight to the pathogenesis of human stone disease."
Tuesday, May 26, 2015
Fly model links zinc to kidney stones, opening possible new routes to prevention and treatment
Chi T, Kim MS, Lang S, Bose N, Kahn A, Flechner L, Blaschko SD, Zee T, Muteliefu G, Bond N, Kolipinski M, Fakra SC, Mandel N, Miller J, Ramanathan A, Killilea DW, Brückner K, Kapahi P, Stoller ML. A Drosophila model identifies a critical role for zinc in mineralization for kidney stone disease. PLoS One. 2015 May 13;10(5):e0124150. PMID: 25970330; PMCID: PMC4430225.
From the abstract: "... Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches."
From the abstract: "... Our findings open a novel perspective on the etiology of urinary stones and related diseases, which may lead to the identification of new preventive and therapeutic approaches."
Thursday, August 7, 2014
Herbal drugs and a Drosophila model of nephrolithiasis (kidney stones)
Wu SY, Shen JL, Man KM, Lee YJ, Chen HY, Chen YH, Tsai KS, Tsai FJ, Lin WY, Chen WC. An emerging translational model to screen potential medicinal plants for nephrolithiasis, an independent risk factor for chronic kidney disease. Evid Based Complement Alternat Med. 2014;2014:972958. PMID: 25097661.
From the abstract: "Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. ... The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0% ... Two herbal drugs ... caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. ..."
From the abstract: "Pharmacological therapy for urolithiasis using medicinal plants has been increasingly adopted for the prevention of its recurrence. A Drosophila melanogaster model developed for translational research of urolithiasis was applied to evaluate agents with potential antilithic effects and calcium oxalate (CaOx) formation. Potential antilithic herbs were prepared in a mixture of food in a diluted concentration of 5,000 from the original extract with 0.5% ethylene glycol (EG) as the lithogenic agent. ... The crystal formation rate in the EG group was 100.0%. In the study, 16 tested herbal drugs reached the crystal formation rate of 0.0% ... Two herbal drugs ... caused the death of all flies. Our rapid screening methods provided evidence that some medicinal plants have potential antilithic effects. ..."
Thursday, January 9, 2014
Flies & kidney disease
Tutor AS, Prieto-Sánchez S, Ruiz-Gómez M. Src64B phosphorylates Dumbfounded and regulates slit diaphragm dynamics: Drosophila as a model to study nephropathies. Development. 2013 Dec 11. PMID: 24335255.
Friday, October 18, 2013
Fly kidney stone model & juices. Recent report.
Ho CY, Chen YH, Wu PY, Chang CH, Chen HY, Man KM, Shen JL, Tsai FJ, Lin WY, Lee YJ, Chen WC. Effects of commercial citrate-containing juices on urolithiasis in a Drosophila model. Kaohsiung J Med Sci. 2013 Sep;29(9):488-93. PMID: 24018152.
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